Experimental studies on animals and on man (such as those reported, for example, in the work "Electronic inhibition and active facilitation of excitability in ventricular muscle" by J. M. Davidenko, M. Delmar, and J. Beaumont in J. Cardiov. Electrophysiol. Vol. 5, No. 11 November 1994, pages 945-960), have shown the effects of subthreshold electrical stimuli on response to subsequent stimulations. These effects are referred to briefly by the term electrotonic inhibition. According to this research, the introduction of a subthreshold conditioning stimulus between two above-threshold stimulations is followed by a transitory decay in the excitability of the muscle stimulated. In particular, a subthreshold stimulus triggered a certain period of time before the subsequent above-threshold stimulus may delay the response to the subsequent stimulus in question, increasing so-called latency, that is, the interval between the pulse and the respective rapid front of the action potential, and even having an actual inhibition effect. The degree of inhibition is directly proportional to the amplitude and to the duration of the subthreshold conditioning stimulus and is inversely proportional to the post-conditioning period between the electrotonic inhibition pulse and the next stimulation pulse.
Electrotonic inhibition can explain some phenomena which occur during atrial fibrillation in man. This applies in particular to the paradoxical effect of a reduction in ventricular frequency due to the action of a vagotonic drug such as digitalis (which reduces atrial refractory periods and therefore considerably increases the frequency of local atrial fibrillation) and to the effect observed, also during atrial fibrillation, of a reduction in the shortest R-R periods of the electrocardiograph signal, to the point of disappearance, when the ventricle is stimulated at longer intervals.
These phenomena can be explained only by electrotonic inhibition which would act on the atrioventricular node, actually reducing its conduction rate as a result of the increased atrial fibrillation frequency and because of the reverse conduction of ventricular stimuli.
In this connection, the following references may be consulted: "On the mechanism(s) of atrioventricular nodal transmission in atrial fibrillation" by F. L. Meijler and J. Jalife in Cardiology 1997; 42(4); pages 375-384, and
"AV nodal function during atrial fibrillation; the role of electrotonic modulation of propagation" by F. L. Meijler, J. Jalife, J. Beaumont, and D. Vaidya in J. Cardiov. Electrophysiol. Vol. 7, No. 9 September 1996, pages 843-861.
Recent tests in which subthreshold stimuli were used to terminate re-entrant ventricular tachycardia, both at local level and by involving the atrioventricular node, with a view to evaluating the optimal site for performing a radio frequency ablation, should also be considered as further support for the hypothesis of the effect of a reduction in the propagation rate and of an extension of the refractory period. The following references should also be referred to in this connection:
"Subthreshold conditioning stimuli prolong human ventricular refractoriness" by J. R. Windle, W. M. Miles, D. P. Zipes, and E. N. Prystowsky, in Am. J. Cardiol. 1986; 57; pages 381-6, and
"Subthreshold stimulation in the region of the slow pathway during atrioventricular node re-entrant tachycardia: correlation with effect of radio-frequency catheter ablation" by S. Willems, C. Weiis, T. Hofmann, C. Rickers, and T. Meinertz in JACC Vol. 29, No. 2, February 1997, pages 408-15.